Methods and compositions for treating and preventing disease associated with alpha-v beta-8 integrin

Abstract

Methods and compositions comprising integrin β8 antibodies are provided.

What is claimed is: 
     
       1. A method of detecting the presence or quantity of integrin β8 in a biological sample, the method comprising
 contacting the biological sample with an antibody and detecting the presence, absence, or quantity of the antibody specifically bound to 138 in the sample, wherein the antibody specifically binds to human integrin β8 and inhibits adhesion of latency associated peptide (LAP) to αvβ8, wherein the antibody comprises: 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:1 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:2 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:3 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:4 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:5 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:6 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:7 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:17; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:8 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:18; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:9 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:19; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:10 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:20; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:11 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:20; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:12 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:20; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:13 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:20; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:14 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:21; or 
 a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:15 and a light chain variable region comprising the complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:22. 
 
     
     
       2. The method of  claim 1 , wherein the antibody is linked to a detectable label. 
     
     
       3. The method of  claim 2 , wherein the label is fluorescent. 
     
     
       4. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:89, HCDR2 comprises SEQ ID NO:24, and HCDR3 comprises SEQ ID NO:25, and 
 LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48. 
 
     
     
       5. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:88, HCDR2 comprises SEQ ID NO:90, and HCDR3 comprises SEQ ID NO:25, and 
 LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48. 
 
     
     
       6. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:89, HCDR2 comprises SEQ ID NO:26, and HCDR3 comprises SEQ ID NO:25, and 
 LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48. 
 
     
     
       7. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:91, HCDR2 comprises SEQ ID NO:93, and HCDR3 comprises SEQ ID NO:29, and 
 LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:49, and LCDR3 comprises SEQ ID NO:50. 
 
     
     
       8. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:92, HCDR2 comprises SEQ ID NO:28, and HCDR3 comprises SEQ ID NO:29, and 
 LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:49, and LCDR3 comprises SEQ ID NO:50. 
 
     
     
       9. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:94, HCDR2 comprises SEQ ID NO:96, and HCDR3 comprises SEQ ID NO:32, and 
 LCDR1 comprises SEQ ID NO:51, LCDR2 comprises SEQ ID NO:52, and LCDR3 comprises SEQ ID NO:53. 
 
     
     
       10. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:95, HCDR2 comprises SEQ ID NO:31, and HCDR3 comprises SEQ ID NO:32, and 
 LCDR1 comprises SEQ ID NO:51, LCDR2 comprises SEQ ID NO:52, and LCDR3 comprises SEQ ID NO:53. 
 
     
     
       11. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:97, HCDR2 comprises SEQ ID NO:99, and HCDR3 comprises SEQ ID NO:35, and 
 LCDR1 comprises SEQ ID NO:54, LCDR2 comprises SEQ ID NO:55, and LCDR3 comprises SEQ ID NO:56. 
 
     
     
       12. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:98, HCDR2 comprises SEQ ID NO:34, and HCDR3 comprises SEQ ID NO:35, and 
 LCDR1 comprises SEQ ID NO:54, LCDR2 comprises SEQ ID NO:55, and LCDR3 comprises SEQ ID NO:56. 
 
     
     
       13. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:100, HCDR2 comprises SEQ ID NO:102, and HCDR3 comprises SEQ ID NO:38, and 
 LCDR1 comprises SEQ ID NO:57, LCDR2 comprises SEQ ID NO:58, and LCDR3 comprises SEQ ID NO:59. 
 
     
     
       14. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:101, HCDR2 comprises SEQ ID NO:37, and HCDR3 comprises SEQ ID NO:38, and 
 LCDR1 comprises SEQ ID NO:57, LCDR2 comprises SEQ ID NO:58, and LCDR3 comprises SEQ ID NO:59. 
 
     
     
       15. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:101, HCDR2 comprises SEQ ID NO:39, and HCDR3 comprises SEQ ID NO:38, and 
 LCDR1 comprises SEQ ID NO:57, LCDR2 comprises SEQ ID NO:58, and LCDR3 comprises SEQ ID NO:59. 
 
     
     
       16. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:103, HCDR2 comprises SEQ ID NO:105, and HCDR3 comprises SEQ ID NO:42, and 
 LCDR1 comprises SEQ ID NO:60, LCDR2 comprises SEQ ID NO:61, and LCDR3 comprises SEQ ID NO:62. 
 
     
     
       17. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:104, HCDR2 comprises SEQ ID NO:41, and HCDR3 comprises SEQ ID NO:42, and 
 LCDR1 comprises SEQ ID NO:60, LCDR2 comprises SEQ ID NO:61, and LCDR3 comprises SEQ ID NO:62. 
 
     
     
       18. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:106, HCDR2 comprises SEQ ID NO:108, and HCDR3 comprises SEQ ID NO:45, and 
 LCDR1 comprises SEQ ID NO:63, LCDR2 comprises SEQ ID NO:64, and LCDR3 comprises SEQ ID NO:65. 
 
     
     
       19. The method of  claim 1 , wherein
 HCDR1 comprises SEQ ID NO:107, HCDR2 comprises SEQ ID NO:44, and HCDR3 comprises SEQ ID NO:45, and 
 LCDR1 comprises SEQ ID NO:63, LCDR2 comprises SEQ ID NO:64, and LCDR3 comprises SEQ ID NO:65.